TLR2 controls intestinal carcinogen detoxication by CYP1A1.

Intestinal cytochrome P450 subclass 1A1 (CYP1A1) contributes to a metabolic "shield" protecting the host from ingested carcinogens such as polycyclic aromatic hydrocarbons (PAH). The expression of CYP1 (including CYP1A2 and CYP1B1) is considered to depend solely on a heterodimeric transcri...

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Autores principales:	Khoa Nguyen Do, Lisbeth Nielsen Fink, Thomas Elbenhardt Jensen, Laurent Gautier, Alexandr Parlesak
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9af26b7866974fa6be10e0dc5d785b51
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spelling	oai:doaj.org-article:9af26b7866974fa6be10e0dc5d785b512021-11-18T07:24:45ZTLR2 controls intestinal carcinogen detoxication by CYP1A1.1932-620310.1371/journal.pone.0032309https://doaj.org/article/9af26b7866974fa6be10e0dc5d785b512012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22442665/?tool=EBIhttps://doaj.org/toc/1932-6203Intestinal cytochrome P450 subclass 1A1 (CYP1A1) contributes to a metabolic "shield" protecting the host from ingested carcinogens such as polycyclic aromatic hydrocarbons (PAH). The expression of CYP1 (including CYP1A2 and CYP1B1) is considered to depend solely on a heterodimeric transcription factor consisting of the arylhydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT). So far, no interference has been noted between the regulation of CYP1 and the activation of Toll-like receptor 2 (TLR2), which modulates the inflammatory response to bacterial cell wall components in immune cells and enterocytes. Here we report that intestinal CYP1A1 is silenced in TLR2-deficient mice, even when under exposure to the carcinogenic PAH benzo[a]pyrene (BaP). In contrast, hepatic CYP1A1 was moderately induced in TLR2-deficient mice without restoring their ability to clear BaP from systemic circulation, as present in wild-type animals. After feeding of BaP for 21 days, only TLR2(-/-) mice, but not their wild type littermates developed polyps in the colon. Gene expressions and protein concentrations of AHR and ARNT in the intestine did not differ between the genotypes. In conclusion, the presence of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance of intestinal microbiota when trying to unravel pathways present in mammals and opens new perspectives for research in human health.Khoa Nguyen DoLisbeth Nielsen FinkThomas Elbenhardt JensenLaurent GautierAlexandr ParlesakPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32309 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Khoa Nguyen Do Lisbeth Nielsen Fink Thomas Elbenhardt Jensen Laurent Gautier Alexandr Parlesak TLR2 controls intestinal carcinogen detoxication by CYP1A1.
description	Intestinal cytochrome P450 subclass 1A1 (CYP1A1) contributes to a metabolic "shield" protecting the host from ingested carcinogens such as polycyclic aromatic hydrocarbons (PAH). The expression of CYP1 (including CYP1A2 and CYP1B1) is considered to depend solely on a heterodimeric transcription factor consisting of the arylhydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT). So far, no interference has been noted between the regulation of CYP1 and the activation of Toll-like receptor 2 (TLR2), which modulates the inflammatory response to bacterial cell wall components in immune cells and enterocytes. Here we report that intestinal CYP1A1 is silenced in TLR2-deficient mice, even when under exposure to the carcinogenic PAH benzo[a]pyrene (BaP). In contrast, hepatic CYP1A1 was moderately induced in TLR2-deficient mice without restoring their ability to clear BaP from systemic circulation, as present in wild-type animals. After feeding of BaP for 21 days, only TLR2(-/-) mice, but not their wild type littermates developed polyps in the colon. Gene expressions and protein concentrations of AHR and ARNT in the intestine did not differ between the genotypes. In conclusion, the presence of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance of intestinal microbiota when trying to unravel pathways present in mammals and opens new perspectives for research in human health.
format	article
author	Khoa Nguyen Do Lisbeth Nielsen Fink Thomas Elbenhardt Jensen Laurent Gautier Alexandr Parlesak
author_facet	Khoa Nguyen Do Lisbeth Nielsen Fink Thomas Elbenhardt Jensen Laurent Gautier Alexandr Parlesak
author_sort	Khoa Nguyen Do
title	TLR2 controls intestinal carcinogen detoxication by CYP1A1.
title_short	TLR2 controls intestinal carcinogen detoxication by CYP1A1.
title_full	TLR2 controls intestinal carcinogen detoxication by CYP1A1.
title_fullStr	TLR2 controls intestinal carcinogen detoxication by CYP1A1.
title_full_unstemmed	TLR2 controls intestinal carcinogen detoxication by CYP1A1.
title_sort	tlr2 controls intestinal carcinogen detoxication by cyp1a1.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9af26b7866974fa6be10e0dc5d785b51
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TLR2 controls intestinal carcinogen detoxication by CYP1A1.

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